The proposed study is concerned with the volume regulatory response of the nucleated red blood cells of amphiuma. The broad objective is to gain a better understanding of how cell volume is regulated by performing studies on this model system. The choice of the amphiuma RBC for the proposed studies relates to the suitability of these cells for studies of membrane electrical events as well as ion flux; both of which are necessary in order to test hypotheses concerning cell volume regulation. The major hypotheses to be tested are that net ion fluxes responsible for cell volume regulation traverse the membrane via electrically silent pathways & that net alkali metal ion flux proceeds in exchange for H while C1 exchanges for HCO3. The above pathways operate in parallel and are functionally linked by the movements of H such that H and HCO3 move in one direction while net alkali metal, chloride and H2O fluxes proceed in the other. Based upon previous studies by myself the above model or its kinetically distinguishable, thermodynamic equivalent will accurately account for and predict ion fluxes during the cell volume regulatory response. The study of cell volume regulation is of interest as a fundamental cellular process which is clinically relevant as it relates to ischemia, hypoxia and impaired cellular metabolism. In addition, preliminary studies suggest that the ion flux pathways responsible for cell volume regulation may also be important in cellular pH regulation as well as Na linked H2O transport by a number of epithelia including the renal tubule.